Background: The major causes of failure after total knee arthroplasty (TKA) include prosthesis loosening and infection. This study aimed to investigate the role of carboxymethyl chitosan (CMC) in knee arthroplasty. Methods: A total of 20 New Zealand white rabbits that were divided into two groups (10 in the control group and 10 in the chitosan group) were included in the study. They underwent TKA surgery, and all were implanted with titanium rod prostheses; the prosthesis in the chitosan group was coated with CMC. After 12 weeks, all rabbits were euthanized, and the following analyses of some specific surface membrane tissues around the prosthesis were performed: X-ray analysis; micro-computed tomography scan; haematoxylin and eosin, Van Gieson, and Von Kossa staining; reverse transcription polymerase chain reaction; and Western Blotting. Results: The result of CCK8 test showed CMC can promote cell proliferation and increase cell viability. Radiological result showed better amount of bone deposits and more bone formation in the chitosan group. HE staining result showed CMC reduces inflammation around the prosthesis. The VG and Von Kossa staining results showed CMC can promote bone deposition around prosthesis. And according to the results of PCR and WB, the OCN content was higher in the chitosan group, while the MMPs content was lower. The chitosan group has an increased OPG/RANKL ratio than the control group. Conclusion: CMC can effectively inhibit the inflammatory response around the prosthesis and osteoclast activation and promote osteogenesis by interfering with the osteoprotegerin/receptor activator of nuclear factor kappa-Β ligand/receptor activator of nuclear factor kappa-Β signalling pathway.

Wear debris induced aseptic loosening is the leading cause of total knee arthroplasty (TKA) failure. The complex mechanism of aseptic loosening has been a major issue for introducing effective prevention and treatment methods, so a simplified yet efficient rabbit model was established to address this concern with the use of micrometer-sized titanium particles. 20 New Zealand white rabbits were selected and divided into two groups (control = 10, study = 10). A TKA surgery was then performed for each of them, with implantation of a titanium rod prosthesis which was coated evenly with micrometer-sized titanium in the study group and nothing in the control group, into right femoral medullary cavity. After 12 weeks, all the animals were euthanized and X-ray analyses, H&E staining, Goldner Masson trichrome staining, Von Kossa staining, PCR, and Western blotting of some specific mRNAs and proteins in the interface membrane tissues around the prosthesis were carried out. The implantation of a titanium rod prosthesis coated with 20 μm titanium particles into the femoral medullary cavity of rabbits caused continuous titanium particle stimulation around the prosthesis, effectively inducing osteolysis and aseptic loosening. Titanium particle-induced macrophages produce multiple inflammatory factors able to activate osteoclast differentiation through the OPG/RANKL/RANK signaling pathway, resulting in osteolysis while suppressing the function of osteoblasts and reducing bone ingrowth around the prosthesis. This model simulated the implantation and loosening process of an artificial prosthesis, which is an ideal etiological model to study the aseptic prosthetic loosening.